Specific scent glands and other biological sources of odor are widespread in the animal kingdom. Olfactory stimuli from these sources are processed by several sensory systems and elicit a range of highly specific behavioral and neuroendocrine responses. Individual components of a particular behavioral sequence may depend upon different individual compounds or blends within a single melange of natural odors. Several different afferent inputs (i.e. the main and accessory olfactory systems) may cooperate in the detection and discrimination of a complex natural odor. In fact, one of the signal features of the olfactory system is its ability to detect and process both the quantitative and qualitative aspects of simple and complex natural stimuli so that appropriate behavioral responses are produced. The neural mechanisms which are responsible for these discriminative abilities, especially those which participate in the resolution of different odor qualities are poorly understood. Moreover, it appears that both the discriminative capabilities of the system and the neural substrates which underlie these abilities are not fixed but remain modifiable throughout life. We assume that the ambient olfactory environment present during the normal, or injury induced, development of an olfactory receptor neuron alters both its relative responsiveness to subsequent odor stimuli and the pattern and extent of its synaptic interactions with second order neurons in the olfactory bulb. We plan to continue our study of olfactory communication in mammals by focusing on the role of chronic odor exposure and receptor neuron turnover in modifying odor quality discrimination in the mouse. We presume that treatments which reliably alter quality discriminations in a predictable fashion will also produce alterations in those regions of the olfactory system that participate in the discrimination of odor quality. Once localized, the neural alterations produced in these regions will be evaluated in order to unravel the neural mechanisms responsible for quality discrimination. In addition to its well recognized ability to make complex olfactory discriminations, the mouse model adds the potential for a range of genetic manipulations and a decrease in normal intra-animal differences. A range of different purified odorous compounds, including behaviorally relevant components of pheromones will be used as stimuli in an integrated series of anatomical and behavioral studies of the olfactory system with the long term goal of revealing how chemical signals ultimately give rise to natural behaviors. Special emphasis will be placed on the roles played by both early and late olfactory experience in shaping the afferent systems and the mechanisms associated with the encoding and processing of pheromone and non-pheromone stimuli. As was the case with our previous proposal, this continues to be a broad program in which we ultimately hope to obtain the complete specification of each odor stimulus, the properties of the various receptors, their central pathways, and the behaviors elicited by chemical signals.